The integration of pharmacogenetic (PGx) testing into primary care is rapidly evolving. It has been estimated that one-fourth of outpatients are taking medications containing PGx information in their product labels, the majority of which are prescribed by primary care physicians. Our previous work from the parent R01 (R01 GM081416, Haga, PI) indicated that the general public is very interested in PGx testing. However, physicians are less enthusiastic about integrating PGx testing into clinical practice, due lack of awareness of available tests, lack of knowledge about genetics and drug response, lack of conclusive clinical evidence, questions about when to order testing and for which drugs or patients, and concerns regarding coverage and reimbursement. Thus, to improve physician knowledge, address issues about how and when to integrate PGx testing into clinical care, and to facilitate integration of PGx testing into therapeutic decision-making this renewal proposal will focus on assessing delivery models of PGx testing. We will implement and evaluate two delivery models of PGx testing into primary care practices: physician-initiated testing and pharmacist-initiated testing. Each practice will be provided an educational intervention (seminars, Intranet module, and pocket guide of drugs with applicable PGx testing). In the physician-initiated group, physicians will also have on-call pharmacist support. In the pharmacist-initiated group, a pharmacist based within the practice will identify prescribed drugs with available PGx testing through chart review and provide specific information and recommendations about PGx testing to the ordering physician. The proposed study aims to evaluate the delivery of PGx testing from three perspectives: physician, patient, and practice setting. Effectiveness of the delivery models will be evaluated by the number of dosage adjustments and adverse responses for new and recent prescriptions (less than 1month) of target drugs and number of office visits in each practice during the 6- month intervention period compared to the 6 months prior to the intervention and the 6 months following the intervention in order to assess change and durability of any changes (Aim 1). Providers in each practice will be surveyed at the start and conclusion of the study to assess changes in knowledge and attitudes of PGx testing and perceived value of and barriers to testing (Aim 2). Similarly, we will follow-up with patients offered PGx testing to explore the perceived value and risks of testing, factors influencing their decision about testing, , and their satisfaction with treatment based on the test result (Aim 3). We will also perform an economic analysis to evaluate and compare the costs associated with each delivery model as well as costs associated with targeted medications, associated monitoring costs, and adverse drug events (Aim 4). These results will provide essential information on the uptake, impact, barriers, and cost of two delivery models for integration of PGx testing in primary care practices. PUBLIC HEALTH RELEVANCE: By increasing physician knowledge and awareness of PGx testing and by providing physicians with primary or secondary pharmacist support on PGx testing, we hope to identify and overcome barriers to the uptake of appropriate PGx testing and to facilitate a seamless integration of PGx testing in primary care practices to improve clinical outcomes.